Nanoparticles (particles with diameters smaller than 1 micron) are ubiquitous and by far the most abundant particle-like entities in natural environments on Earth and are widespread across many applications associated with human activities. There are many types of naturally occurring nanoparticles and man-made (engineered) nanoparticles. Nanoparticles are found in the air, in aquatic environments, in rain water, in drinking water, in bio-fluids, in pharmaceuticals, and in drug delivery and therapeutic products, and a broad range of many industrial products. Nanoparticles usually occur within poly-disperse assemblages, which are characterized by co-occurrence of differently-sized particles, including those larger in thediameter than 1 micron.
Given the widespread usage of nanoparticles, the ability to control and accurately characterize their properties may be useful to many applications. Conventional methods for measuring nanoparticle properties may be inaccurate for poly-disperse samples of mixed nanoparticle sizes, which are common in many applications. Because the light scattered from all nanoparticles is measured simultaneously, it may be difficult to resolve the nanoparticles into their constituent sizes when there is a range of particle sizes. Other approaches fail to account for the large differences in the intensity of scattered light produced by differently-sized nanoparticles across the range of nanoparticle sizes. In these approaches, the low scattering signals from small nanoparticles may be undetected, or the high scattering signals from larger nanoparticles can obscure the signals from smaller nanoparticles. And in yet other approaches, the measurements fail to account for the growth rate or dissolution rate of the particles, such that a snap-shot of a size distribution could be inaccurate a few moments later. As a result of these deficiencies, the concentration of nanoparticles of any given size, and hence the entire size distribution, can be subject to unknown error.
These methods of detecting nanoparticles (and larger particles) are commonly referred as dark field microscopy. The instrument to perform such an analysis typically comprises a small cell (for example a cuvette) that enables illumination of a liquid with a precisely-defined, narrow light sheet and observation of the scattered light from the nanoparticles, usually (but not necessarily) at a 90-degree angle relative to the light sheet plane. It should be noted that the angle of observation need not be 90 degrees; what is important is that the scattered light is observed. Different sizes of particles can be visualized via the camera capturing light scattered by particles, with images having different sizes and intensities (various brightness of pixels) depending on the size of the particles.
In U.S. patent application Ser. No. 14/730,138, filed on Jun. 3, 2015, titled “NANOPARTICLE ANALYZER” (“Stramski”), the entirety of which is incorporated herein by reference, these problems were addressed by using several light sources and a single-color camera recording simultaneously several different colors of scattered light by the Bayer pattern of pixels corresponding to the three additive primary colors conventionally used in photography. In the Stramski approach, final images were obtained from a single recording device, and hence images of the same colloidal volume at different colors were recorded in the same area of the recording device or sensor, thereby resulting in pixel numbering relative to a single point of origin, usually being one of the corners of a sensor in the camera. This made processing images in different colors possible because positions of observed particles were given in the same system of coordinates. Unfortunately, Stramski does not discuss or disclose any methods to account for the growth or dissolution of the particles.
U.S. application Ser. No. 15/018,532 filed on Feb. 8, 2016, titled “MULTI-CAMERA APPARATUS FOR OBSERVATION OF MICROSCOPIC MOVEMENTS AND COUNTING OF PARTICLES IN COLLOIDS AND ITS CALIBRATION” (“Tatarkiewicz”) overcomes some of the deficiencies of Stramski by introducing a calibration mask and method that can align the images from various light sources such that processing of the images is made more accurate. But again, Tatarkiewicz does not discuss or disclose any methods to account for the growth or dissolution of the particles.
The growth/dissolution of particles can be of particular interest is various industries. For example, a pharmaceutical company may want to confirm that its drug dissolves at a particular rate such that it can be used in an effective time-release mode. Moreover, such a dissolution may be most therapeutically effective when the particles dissolve to the nanoscale and does not re-combine to grow into larger particles. Another pharmaceutical company may need to determine the time needed to crystallize a new drug based on protein that can be delivered in higher doses as large crystals. So, while the methods and apparatuses disclosed in Stramski and Tatarkiewicz may be helpful in obtaining a snapshot of the particle size distribution of the drug, it is not helpful in providing a dissolution rate (or conversely a growth rate).
What is needed, therefore, is an improved system that effectively measures the growth/dissolution kinetics of colloidal particles.